Several new antigens discovered in our laboratory revealed the existence of at least 9 gene-clusters which have in common that they control murine lymphocyte surface alloantigens. Immunogenetic analysis of the two of these gene clusters, i.e. Ly-ml1-H-3-beta-2-microglobulin (B2m) genes on chromosome 2 and M1s-Ly-m20-Ly-m21 genes on chromosome 1, is the subject of this grant proposal. The H-3 and B2m antigens have been linked together since the establishment of the Ly-m11 alloantigen system, which is most likely an allotype of mouse beta-2-microglobulin. Formal genetics of the Ly-m11 alloantigen system will reveal the close relationship or identity of Ly-m11, H-3 and B2m on chromosome 2. Regulation of Ly-m11 antigen expression by a gene(s) linked to the Tla locus will be studied. Detection of the Ly-m11 antigen in body fluids will lead to immunochemical studies to compare cell-surface associated and water-soluble molecules including amino acid sequences. By using killer target cell interaction and anti-H-3 cytotoxic T lymphocytes, a crucial role of the Ly-m11 antigen in cell recognition phase will be clarified. Moreover, the effects of passively administered anti-Ly-m11 antibodies on the skin graft or tumor grafts will be studied and may reveal the deep concern of the Ly-m11 molecule with transplantation immunology. Studies of the M1s-Ly-m20-Ly-m21 gene cluster on chromosome 1 will be focused on the relationship between these three gene products, i.e. lymphocyte defined (LD) mixed lymphocyte stimulating antigen, M1s, serologically-determined (SD) B-cell alloantigen Ly-m20 and T-cell alloantigen Ly-m21. Gene product(s) of M1s locus will be characterized by MLC blocking with anti-Ly-m20 antibodies. The knowledge of M1s-mediated reactions can shed light on the lymphocyte activation. The two new cell surface markers Ly-m20 and Ly-m21 will be useful for the studies of ontogeny of mouse B-cell or T-cell differentiation lineages. Also, the Ly-m21 (a selective T-cell antigen) antigenic marker will be used for the functional analysis of lymphocyte subsets, i.e. helper, suppressor or cytotoxic killer cells. Chemical characterization of Ly-m20 and Ly-m21 antigens will be essential for the understanding of the relationship between gene products of M1s region, viz, LyM-1, Lgp 100, Ly-9, and T100.